The preterm parturition syndrome

The implicit paradigm that has governed the study and clinical management of preterm labour is that term and preterm parturition are the same processes, except for the gestational age at which they occur. Indeed, both share a common pathway composed of uterine contractility, cervical dilatation and activation of the membranes/decidua. This review explores the concept that while term labour results from physiological activation of the components of the common pathway, preterm labour arises from pathological signalling and activation of one or more components of the common pathway of parturition. The term 'great obstetrical syndromes' has been coined to reframe the concept of obstetrical disease. Such syndromes are characterised by: (1) multiple aetiology; (2) long preclinical stage; (3) frequent fetal involvement; (4) clinical manifestations that are often adaptive in nature; and (5) gene–environment interactions that may predispose to the syndromes. This article reviews the evidence indicating that the pathological processes implicated in the preterm parturition syndrome include: (1) intrauterine infection/inflammation; (2) uterine ischaemia; (3) uterine overdistension; (4) abnormal allograft reaction; (5) allergy; (6) cervical insufficiency; and (7) hormonal disorders (progesterone related and corticotrophin-releasing factor related). The implications of this conceptual framework for the prevention, diagnosis, and treatment of preterm labour are discussed.     

Crossover use of donated blood for autologous transfusion: report of the Council on Scientific Affairs, American Medical Association

BACKGROUND: Controversy exists concerning whether the costs and potential risks outweigh the potential benefits of "crossover" use in the general blood supply of unutilized blood that was donated for autologous transfusion. STUDY DESIGN AND METHODS: Published articles and reports were identified through systematic search of MEDLINE and review of references cited in previously identified articles, textbooks, and reports. Consultation was made with experts in blood donation and transfusion. Additional peer review was received from the American Medical Association (AMA) Council on Scientific Affairs RESULTS: Concern over infectious disease transmission has led to increased interest in and support for autologous transfusion for individuals having planned surgeries. Different requirements exist for collection, labeling, and screening of blood to be used for autologous versus allogeneic transfusions; therefore, procedures for diverting autologous blood donations to the general blood supply involve considerable expense. Several cost-effectiveness studies of autologous blood donation and transfusion conclude that currently this "crossover" appears to be an expensive procedure yielding little increased benefit from a societal perspective. CONCLUSIONS: The recommendations in this report were adopted as AMA Policy at the AMA Annual Meeting in June 1997. The AMA does not encourage blood collection programs to "cross over" units donated for autologous use to the allogeneic blood supply. Practice guidelines are needed, and should be utilized to ensure parsimony in the use of autologous blood donations and transfusions.     

Granulocyte transfusions: efficacy in treating fungal infections in neutropenic patients following bone marrow transplantation

Background: A retrospective study was conducted to evaluate the efficacy of granulocyte transfusions in neutropenic patients with fungal infections following bone marrow transplantation. Study Design and Methods: Systemic fungal infection was detected in 87 patients during the first 100 days following bone marrow transplantation; 50 received granulocytes in addition to appropriate antifungal agents. The median age was 17 years in the transfused patients (range, 1.5–57) and 35 years in the nontransfused patients (range, 0.8–50). Granulocyte transfusions were given on a daily to twice-daily basis. To evaluate their responses, patients were categorized by infection type (candidal [n = 38] vs. noncandidal [n = 49]) and site (fungemia alone [n = 30] vs. invasive infection [n = 57]). Resolution of infection was defined as the resolution of signs and symptoms and negative cultures and/or histopathology. Results: No benefit of granulocyte transfusions could be shown in the resolution of infection in patients with either invasive noncandidal infection (29% in the transfused patients vs. 23% in the nontransfused patients, p > 0.1) or candidal sepsis (56% vs. 50%, p > 0.1). Among patients with delayed marrow recovery, no difference was seen in the resolution of infection in the transfused (25.9%) and nontransfused (50%) patients (p > 0.1); nor was any difference between the transfused and nontransfused patients evident in the duration of febrile episode associated with the fungal infection. Granulocyte transfusions were well tolerated, with the only complications being fever in 12 patients (24%), chills in 10 (20%), and respiratory distress in 2 (4%). Despite attempts to stratify by infection type, invasiveness, and marrow recovery, it was not possible to show any benefit of granulocyte transfusions in this group. Conclusions: It is likely that only through a prospective randomized trial can the question of the efficacy of granulocyte transfusions in treating fungal infections be conclusively answered.     

Protection of human polymorphonuclear leukocyte function from the deleterious effects of isolation, irradiation, and storage by interferon-gamma and granulocyte-colony-stimulating factor

BACKGROUND: Fungal infections represent a difficult challenge to clinicians caring for neutropenic patients with hematologic malignancies, as antifungal therapy often has limited success in that setting. One promising yet problematic alternative approach is leukocyte transfusion. The isolation of polymorphonuclear leukocytes (PMNs) induces apoptosis and functional deterioration, and irradiation to prevent transfusion-associated graft-versus-host disease causes further functional deterioration. STUDY DESIGN AND METHODS: The ability of interferon-gamma and granulocyte-colony-stimulating factor (G-CSF), used both alone and in combination, to protect PMNs after 0 or 20 hours' storage in cell culture (as a model for function after transfusion) and irradiation with 0, 5, or 30 Gy was studied. RESULTS: Without cytokine treatment, 20-hour-old PMNs showed marked apoptosis, no appreciable chemotaxis, and no ability to kill Candida albicans. In contrast, cytokine treatment significantly reduced apoptosis and protected chemotaxis, C. albicans killing, and surface-receptor expression from both storage and irradiation. Although the majority of the benefit appeared to be due to G-CSF, consistent trends suggested better function of PMNs after combined treatment with interferon-gamma and G-CSF. CONCLUSION: Judicious use of cytokines may preserve PMN function. These findings have important implications for the transfusion of PMNs to cytopenic patients.     

Buffy coat platelets stored in apyrase, aprotinin, and ascorbic acid in a suspended bag: combined strategies for reducing platelet activation during storage

BACKGROUND: Platelet activation is an important factor impeding the clinical effectiveness of platelet transfusions. In this study, platelet concentrates (PCs) were prepared by a novel suspended-bag buffy coat technique that was followed by the addition of a mixture of platelet activation inhibitors to the storage bag. STUDY DESIGN AND METHODS: In vitro platelet function was evaluated in PCs prepared by the suspended-bag buffy coat technique and stored at 22 degrees C for 5 days in the presence of (n = 12) or absence (n = 12) of apyrase, ascorbic acid, and aprotinin (AAA). RESULTS: Platelets from AAA- incubated PCs demonstrated mean ATP levels 17 percent (p < 0.004), 13 percent (p < 0.02), and 22 percent (p < 0.003) higher than those measured in parallel control PCs on Days 1, 3, and 5, respectively. Similarly, on Days 3 and 5 of storage, respectively, 45-percent (p < 0.001) and 50-percent (p < 0.001) greater ADP-induced maximum aggregation was observed in AAA-incubated PCs than was seen in control preparations. AAA-incubated PCs demonstrated alpha-granule membrane protein-140 expression 92 percent (p < 0.01), 133 percent (p < 0.003), and 104 percent (p < 0.001) below that in control PCs on Days 1, 3, and 5, respectively. At similar intervals, a significant increase in recovery from hypotonic shock also was observed in AAA-incubated PCs. Further, Day 5 AAA-PCs demonstrated significantly higher morphology scores and O2 consumption than did control preparations. CONCLUSION: Buffy coat platelets prepared in suspended bags and stored in the presence of AAA demonstrate significantly reduced activation and enhanced functional and metabolic activity.     

American Red Cross experience with routine testing for hepatitis B core antibody

The implementation of routine testing of blood donations for hepatitis B core antibody (anti-HBc) has allowed the characterization of the performance of the test in a large number of samples from apparently healthy individuals. This study reports the experience of the American Red Cross in testing 2.3 million donors for anti-HBc. The test protocol reproducibly identified a distinct population of donors. The anti-HBc-positive rate varied by region of the continental United States and by the time of year. In a case-control study, 85 percent of subsequent donations from anti-HBc-positive donors were anti-HBc positive. The predictions made in an earlier pilot study regarding the performance and impact of the test were borne out.     

Influence of the HLA-DRB1 locus on susceptibility and severity in rheumatoid arthritis

We examined HLA-DR genotype risk in 288 patients with rheumatoid arthritis who were carefully categorized for disease severity. Five hundred ethnically-matched bone-marrow donors were controls. A hierarchy of positive allelic associations was noted with DRB1*0401 (p < 10(-38), *0404,8 (p < 10(-43), *0405 (p < 10(-8), *10 (p < 10(-3) and *0101,2 (p < 10(-2), while DRB1*0403 was negatively associated (p = 0.02). The DRB1 genotype relative risks (and 95% CIs) for RA were: *0404,5,8/*0404,5,8 = 36.2 (15-87), *0401/*0404,5,8 = 31.3 (18-55), *401/*0401 = 18.8 (11-35), *0101,2/*0404,5,8 = 6.0 (2-14), *0101,2/*0401 = 6.4 (3-12), *0101,2/*0101,2 = 1.3 (0.3-6), *10/*0404,5,8 = 27.8 (5-148), *10/*0401 = 20.8 (5-89), *10/*0101,2 = 22.3 (5-96), *0404,5,8/DRX = 5.0 (3-8), *0401/DRX = 4.7 (3-7), *0101,2/DRX = 2.3 (1.4-4), *10/DRX = 3.4 (0.8-14). No significant correlation of DRB1 genotypes was found with severity of RA as judged by nodules or articular erosions.